This application is in support of Dr Gajic's career development as an independent clinical investigator. Dr Gajic has recently completed a Master's Program in Clinical Research at the Mayo Clinic College of Medicine. During the award period, Dr Gajic will advance his research training with particular focus on medical informatics and apply the lessons of didactic teaching and practical experiences in applied physiologic, laboratory methods and clinical outcome assessment towards a comprehensive clinical research project. In an observational cohort study of mechanically ventilated patients, Dr. Gajic has recently identified transfusion of blood products and ventilator settings as major risk factors for the development of acute lung injury. The proposed prospective research builds on these observations. Transfusion Related Acute Lung Injury (TRALI) has been largely under-diagnosed and under-reported because of a lack of sensitive and specific diagnostic criteria. Based on case series, it has been proposed that anti-leukocyte antibodies and mediators of inflammation in donor blood trigger a pulmonary immune response in primed or susceptible hosts. However, to date this hypothesis has not been validated in a prospective clinical trial. It is Dr Gajic's long-term objective to delineate the role of blood transfusions and mechanical forces in the pathogenesis of acute lung injury and to develop an effective preventive strategy. In a prospective cohort of critically ill medical patients he aims to (1) determine the incidence and outcome of acute lung injury which develops in temporal association with blood transfusion in the medical intensive care unit;(2) determine if donor gender, type of blood product and storage age are associated with an increased risk of TRALI;and (3) to compare the prevalence of anti-leukocyte antibodies (anti-granulocyte, anti-HLA class I and II) and the amount of inflammatory cytokines (IL 6, IL 8 and TNF) in donor blood samples of patients with and without a TRALI compatible event. These results will form the basis for future trials with major public health implications. (End of Abstract)